Prenatal diagnosis of fetal bradyarrhythmia and postnatal outcome

Abstract

Introduction

Prenatal diagnosis of Fetal bradyarrhythmia leads to parental and care provider anxiety as data on outcome is scarce. We aimed to correlate the prenatal presentation of fetal bradyarrhythmia with postnatal outcome.

Methods

Retrospective analysis of case records from 2017 to 2021. All fetuses with sustained bradyarrhythmia beyond 11 weeks were included in the study.

Results

Twenty fetuses were identified: mean gestational age at diagnosis was 23 weeks 2 days. The type of bradyarrhythmia was as follows: Complete atrioventricular block 10 (50 %), Sinus Bradycardia 7 (35 %), second degree atrioventricular block 2 (10 %), and Unclassified 1 (5 %). In 10 fetuses, cardiac and extracardiac anatomy were normal; 8 fetuses (40 %) had cardiac anomalies,1 fetus had intraventricular hemorrhage and 1 had nuchal cystic hygroma. Among the fetuses with associated anomalies, there were 5 terminations of pregnancy (TOP), 1 intrauterine fetal demise (IUD), 3 neonatal demise (NND) and 1 livebirth. Among fetuses with normal anatomy, there were 2 TOP and 8 livebirths; five of the 10 mothers (50 %) tested positive for Anti Ro/La antibodies. All the 6 liveborn fetuses with complete atrioventricular block are on conservative management: 2 on metaproterenol and 4 on clinical follow up. Nine out of the 10 cases that had a postnatal paediatric cardiology assessment had a correct prenatal diagnosis.

Conclusion

Correct prenatal identification of fetal bradyarrhythmia is feasible in about 90 % of cases. The risk of postnatal pacemaker requirement appears to be low irrespective of maternal Anti Ro/La status.

Abbreviations

AVB

- Atrioventricular Block

AVSD

- Atrioventricular Septal Defect

Bpm

- Beats per minute

CAVB

- Complete Atrioventricular Block

CHD

- Congenital Heart Disease

CNS

- Central Nervous System

IUD

- Intrauterine demise

LSVC

- Left Superior Venacava

NND

- Neonatal demise

NT

- Nuchal Translucency

PACE

- Perinatal Adverse Clinical Events

TOP

- Termination of pregnancy

VHR

- Ventricular Heart Rate

1. Introduction

Fetal arrhythmias are uncommon complicating about 1–2% of pregnancies and constituting about 10 % of referrals to fetal medicine and cardiology units [1,2]. Despite the advances in technology, fetal arrhythmias pose a diagnostic challenge for prenatal physicians and a disturbing finding for prospective parents. Fetal bradycardia is defined as a heart rate ≤110 bpm and is said to be sustained when there is persistent bradycardia during the examination period of 45 min [3,4]. The mechanism underlying the bradyarrhythmia can be sinus bradycardia, blocked premature atrial contractions or atrioventricular block [2,5]. Prognosis depends on the etiology of bradyarrhythmia, recognition of associated anomalies, and degree of cardiac dysfunction. Data on the postnatal outcome in prenatally diagnosed fetal bradyarrhythmia appear to be scarce from the Indian sub-continent. This paper aims to present the prenatal presentation of fetal bradyarrhythmia along with parent-reported postnatal outcome.

2. Methods

2.1. Study design

This was a retrospective observational study performed at a regional referral centre for Fetal Medicine in South India. All fetuses with bradyarrhythmia during the study period of 5 years, from January 2017 through December 2021 were included. Fetal bradyarrhythmia was defined as ventricular heart rate less than 110 beats per minute [3,4]. The bradycardia was considered sustained if it was present throughout the scanning period, at least for 45 min. Fetuses with transient sinus bradycardia and those below 11 weeks gestation were excluded.

As a protocol, the fetal heart rate was measured routinely in the umbilical artery. Any abnormality in rate or rhythm was further evaluated with detailed and dedicated fetal cardiac structural and functional assessment by specialist fetal medicine consultants accredited by the Fetal Medicine Foundation. A detailed fetal anatomical evaluation and fetal echocardiography were done as per the protocols laid down by the International Society for Ultrasound in Obstetrics and Gynaecology. For rhythm assessment, spectral Doppler of the umbilical artery, m-mode assessment at the bi-atrial, bi-ventricular, and atrio-ventricular insonations were used. The examination was performed using Voluson E6 (GE medical systems, Zipf, Austria) and DC 80 (Mindray, Mindray Medical International Limited, Guangdong, China) with anatomic M-mode facilities. Images, measurements and examination notes from each study was entered into an electronic fetal database (Fig. 1).

Fig. 1.

M-mode examination of atrioventricular mechanical events showing complete dissociation between atrial contractions (long arrow) and ventricular contractions (arrowhead) indicating complete AV block in panel A; atrial rate twice the ventricular rate indicating 2:1 AV block in panel B; atrial rate and ventricular rate at 1:1 conduction indicating sinus bradycardia in panel C

2.2. Data collection

The case records were identified in the electronic database and the following data were abstracted onto a preformed electronic spreadsheet: patients’ demographic details, medical comorbidities and autoimmune conditions, history of any drug intake, previous obstetric history and outcome, ultrasound findings of the current pregnancy including cardiac and extracardiac findings at presentation and on follow up visits, fetal therapy and interventions. Mothers with fetal bradyarrhythmia who tested positive for autoimmune antibodies were offered transplacental therapy with Dexamethasone 4 mg BD initially. Intrapartum and neonatal details including postnatal investigations and treatment were entered into the database based on the information provided by the parents. At the time of every clinical visit, each patient signs a form consenting to their pregnancy data being analysed for scientific purposes within the prevailing ethical framework. An ethical committee approval was not sought as this was a retrospective review of data collected for clinical purposes.

2.3. Data analysis

The primary outcome was Perinatal Adverse Clinical Events (PACE) – a composite event that included Termination of Pregnancy (TOP), Intrauterine Fetal Demise (IUD) and Neonatal Demise (NND). The data were analysed using Microsoft Excel. Continuous variables were expressed as Mean/Median with Standard deviation/Range and Categorical variables were expressed as numbers and percentage.

3. Results

We identified 20 fetuses with a diagnosis of bradyarrhythmia during the study period. The mean gestational age at diagnosis was 23.4 weeks. The demographic details of the patient and pregnancy data are shown in Table 1 and Table 2 respectively. The median ventricular heart rate was 65 beats per minute (range, 54–95).

Table 1.

Baseline characteristics: N = 20.

Age in years (Mean, range)		25.35 (18–34)
Body Mass index in kg/m2 (Mean, range)		28.33 (19.7–40)
Parity	Nulliparous (n, %)	12 (60)
	Multiparous (n, %)	8 (40)
Consanguineous marriage (n, %)		2 (10)
Maternal Diabetes	Pre Gestational Diabetes Mellitus (n, %)	2 (10)
	Gestational Diabetes Mellitus (n, %)	1 (5)
Maternal chronic hypertension (n, %)		0 (0)
Hypothyroidism (n, %)		2 (10)
Gestational age at diagnosis in weeks (Mean, range)		23.4 (11.9–36.3)
Prior history of same anomaly (n, %)		0 (0)

Table 2.

Outcome data.

Pregnancy outcome	Termination of pregnancy (n, %)	7(35)
	Stillbirth (n, %)	1 (5)
	Neonatal demise (n, %)	3 (15)
	Livebirth (n, %)	9 (45)
Gestational age at delivery in weeksa (Mean, range)		37.2 (33.7–40)
Mode of deliverya	Vaginal (n, %)	5 (38.5)
	Abdominal (n, %)	8 (61.5)
Birth weight in gramsa (Mean, range)		2592.31(1800–3500)
Gender at birtha	Male (n, %)	8 (61.5)
	Female (n, %)	5 (38.5)
Type of bradyarrhythmia	Complete AV block (n, %)	10 (50)
	Sinus bradycardia (n, %)	7 (35)
	2:1 AV block (n, %)	2 (10)
	Unclassified (n, %)	1 (5)
Associated anomalies	Normal anatomy (n, %)	10 (50)
	Cardiac anomaly (n, %)	8 (40)
	CNS anomaly (n, %)	1 (5)
	Lymphatic anomaly (n, %)	1 (5)
Postnatal follow upb	Clinical follow up (n, %)	6 (66.7)
	Medical management (n, %)	3 (33.3)
	Pacemaker placement (n, %)	0 (0)
Perinatal Adverse Clinical Event (PACE)	In structurally abnormal fetuses	9/10 (90 %)
	In structurally normal fetuses	2/10 (20 %)

^aTermination of pregnancy not included.

^bOnly livebirths included.

The type of bradyarrhythmia was as follows: Complete Atrioventricular block (CAVB) 10 (50 %), Sinus Bradycardia 7 (35 %), Second degree Atrioventricular block (AVB) 2 (10 %), and Unclassified 1 (5 %).

In 10 fetuses, cardiac and extracardiac anatomy was normal while 10 fetuses had associated anatomic abnormalities.

3.1. Fetuses with associated anomalies

In this group of 10 fetuses, 8 fetuses had associated cardiac anomalies. There were two fetuses with extracardiac anomaly - 1 fetus had Central Nervous System (CNS) abnormality (intraventricular hemorrhage and arrest of cortical maturation with cardiac biventricular dysfunction) and 1 had large Nuchal translucency (NT) with cystic hygroma. The most common cardiac abnormality was heterotaxy syndrome (n = 4). The other cardiac defects were atrioventricular septal defect (AVSD) (n = 2), complex cardiac defect (n = 1) and asymmetry of chambers with narrow aortic origin along with persistent left superior vena cava (LSVC) (n = 1).

The type of bradyarrhythmia in this group was as follows: 6 sinus bradycardia, 2 CAVB, one 2:1 AVB, and 1 unclassified.

There were five pregnancy terminations - 3 with heterotaxy syndrome, 1 with complex cardiac defect and 1 with cystic hygroma; one intrauterine fetal demise at 33 weeks with heterotaxy syndrome and hydrops at presentation; three neonatal demise - 2 babies with AVSD (died in the early neonatal period) and one with antenatal intraventricular hemorrhage (delivered at 37 weeks and expired 6 h after birth); one liveborn - under follow up for asymmetry of outflow tracts with persistent LSVC. The rate of PACE in this group was 90 %

3.2. Fetuses with normal anatomy

In this group with normal anatomy (n = 10), there were two pregnancy terminations – both had CAVB; eight livebirths – 6 with CAVB, 1 with 2:1 AVB and 1 with sinus bradycardia.

3.3. Stratification of cases according to gestational age

The cases were also stratified according to the gestational age at diagnosis, i.e., before or after 18 weeks gestation.

Before 18 weeks:

Of the 20 fetuses, 3 were diagnosed before 18 weeks – all 3 fetuses had associated defects: 1 with cystic hygroma, 1 with complete atrioventricular septal defect, and 1 fetus with heterotaxy syndrome.

Beyond 18 weeks:

17 fetuses were diagnosed with fetal bradyarrhythmia beyond 18 weeks and they were distributed as follows:

• •Sinus bradycardia – 6 (3 with complex cardiac defect (TOP), 1 with antenatal intraventricular hemorrhage (neonatal demise), 1 with asymmetry of outflow tracts with persistent LSVC (under follow up), 1 with normal anatomy and subsequently changed to CAVB on postnatal evaluation.)
• •Second degree heart block – 2 (one intrauterine fetal demise at 33 weeks with heterotaxy syndrome and hydrops at presentation, one with normal anatomy and immune mediated reverted to normal rhythm after 6 weeks of antenatal steroid therapy)
• •CAVB – 9 (one with AVSD had neonatal demise on PND 6 due to suspected sepsis, 8 fetuses with normal anatomy[2 TOP, 6 liveborns])

3.4. Livebirths

In total, there were 12 fetuses which were liveborn. Three babies died in the early neonatal period - 2 babies with AVSD and one with antenatal intraventricular hemorrhage. In total, there were 9 survivors among the 12 livebirths.

None of the mothers had a pre-gestational diagnosis of connective tissue disorders. There was no history of any maternal intake of beta blockers, dexamethasone administration, recurrent miscarriage, prior history of fetal bradyarrhythmia, or sudden demise in young relatives.

Antibody testing (anti-Ro, anti-La) was offered to all mothers with fetuses having bradyarrhythmia and normal cardiac anatomy. Out of the 10 mothers for whom testing was advised, four declined. Of the six that were tested, five returned positive (83 %). All the five mothers positive for autoimmune antibodies were started on oral dexamethasone 4 mg twice daily tapered down to 4 mg once daily over 4 weeks as per our unit protocol.

One mother with anti-Ro antibodies on antenatal testing was diagnosed subsequently with systemic lupus erythematosus (SLE). In her subsequent pregnancy, she delivered an unaffected fetus.

All the 6 liveborn surviving infants with CAVB are on conservative management: 2 on metaproterenol and 4 on clinical follow up. None of them required pacing so far. The median age at follow up was 32 months (27–33).

One fetus with 2:1 AVB detected at 21.4 weeks of gestation, reverted to normal rhythm after 6 weeks of antenatal steroid therapy. Postnatally, the neonate had normal rhythm. The mother had tested positive for Anti Ro antibodies. In one fetus, the prenatal diagnosis of sinus bradycardia was subsequently changed to CAVB on postnatal evaluation.

In those where a postnatal diagnosis was established by a paediatric cardiology unit, prenatal diagnosis matched postnatal diagnosis in 9 out of 10 cases.

4. Discussion

In our study, of the 20 fetuses with bradyarrhythmia, 50 % had associated congenital malformations. About 80 % of mothers who opted to get tested for antibodies returned positive in the normal anatomy group. PACE rate was 90 % in fetuses with coexistent anomalies while it was 20 % in fetuses with normal structural evaluation.

The most common mechanism of fetal bradycardia in our study was complete atrioventricular block (50 %). This is consistent with other prior studies [[6], [7], [8], [9]]. Previous studies have shown that 50–60 % of the fetuses with bradyarrhythmia had associated CHD [[9], [10], [11]]. Left atrial isomerism was the most common cardiac defect followed by transposition of great arteries and AVSD [7,[11], [12], [13]]. In our study, the most common CHD associated with fetal bradyarrhythmia was heterotaxy syndrome. Overall, 80 % of adverse perinatal events occurred in the group with underlying CHD. This is in accordance with previous published data [11,13,14].

In the structurally normal group, 4 out of the 10 mothers had opted out of antibody testing. In the remaining mothers, 83 % tested positive for anti Ro/La antibodies, consistent with previous published data [11,[15], [16], [17]]. Transplacental steroid therapy has not been consistently shown to improve outcome in well-resourced settings [11,16]. However there may be improvement in outcome related to mitigation of myocarditis independent of its effect on rhythm [17]. In our series, all immune mediated fetal bradyarrhythmia was treated with transplacental steroids since the time of diagnosis. Of the 5 fetuses with immune mediated bradycardia in our study, 3 had CAVB, 1 had 2:1 AVB and 1 had sinus bradycardia. Fetus with 2:1 AVB reverted to normal sinus rhythm after 6 weeks of steroid therapy and had normal rhythm postnatally. Reversal of AVB to normal sinus rhythm have been reported earlier in literature [18,19]. However less success has been reported in reverting CAVB [16]. In our data, one fetus which was reported antenatally as sinus bradycardia turned out to be CAVB in the postnatal period. All the other mechanisms of bradycardia reported antenatally corresponded with the postnatal diagnosis.

The live birth rate in fetuses with normal anatomy was 80 % in the present study which is similar to previous studies [14,16,17]. Prior studies have reported hydrops as an independent poor prognostic factor for perinatal outcome [11,13,15,16,20]. Of the two cases with hydrops in our study, one underwent pregnancy termination and the other experienced in utero fetal demise. While some studies have reported ventricular heart rate (VHR) < 55 bpm to be associated with poor perinatal outcome [7,9,15,16,21], few other studies have not shown any correlation between VHR and perinatal outcome [13,22]. In one fetus with CAVB, the ventricular rate was 48 bpm and the mother was offered Salbutamol in addition to Dexamethasone, however she deferred taking beta agonist and continued only on steroid.

Of note is the requirement of pacemaker postnatally in our series. Other previous studies have reported pacemaker placement in 25–75 % of bradyarrhythmic fetuses [8,14,16,21,22]. In our series, among 9 alive children on follow up, none of them required pacing till now. This may be attributable to the smaller number of cases.

4.1. Strengths and limitations

The strength of our study was the decreased interobserver variability as this is a single centre study and all cases were analysed only by one of the two Senior Consultants according to our standard operating protocol. This enabled consistency in the final diagnosis. The antenatal diagnosis was also correlated with postnatal diagnosis which was correct in 90 % of cases.

The main limitations are the retrospective nature of the study and the small sample size as data is from a single centre. Data regarding the growth, cardiac performance are not included in this series. Skog et al. reported decreased growth velocity in infants born with II/III degree/Complete AVB [23]. Though postnatal findings and outcome were assessed, a direct face to face evaluation of baby and review of ECG and Echocardiography findings were not feasible as patients were from different location and had postnatal follow up at different places and hospitals.

This study demonstrates that accurate prenatal diagnosis of underlying mechanism of fetal bradyarrhythmia is largely possible and presents data in counseling prospective parents when faced with prenatal diagnosis of bradyarrhythmia. Given the rarity of the condition, most of the previous data from literature are small scale. A multicentric prospective study designed to specifically identify further prognostic factors is needed.

5. Conclusion

Correct prenatal identification of fetal bradyarrhythmia is feasible in about 90 % of cases. Presence of an underlying CHD is a poor prognostic indicator of perinatal outcome. The outcome in fetuses with normal cardiac anatomy is favourable, with close to 80 % intervention free survival by 2.5 years of age. In structurally normal fetuses, the risk of postnatal pacemaker requirement appears to be low irrespective of maternal Anti Ro/La status. A multidisciplinary team-based approach is necessary to best optimize the pregnancy outcome.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.